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The best management of patients who suffer from traumatic brain injury (TBI) while on oral anticoagulants is one of the most disputed problems of emergency services. Indeed, guidelines, clinical decision rules, and observational studies addressing this topic are scarce and conflicting. Moreover, relevant issues such as the specific treatment (and even definition) of mild TBI, rate of delayed intracranial injury, indications for neurosurgery, and anticoagulant modulation are largely empiric. We reviewed the most recent evidence on these topics and explored other clinically relevant aspects, such as the promising role of dosing brain biomarkers, the strategies to assess the extent of anticoagulation, and the indications of reversals and tranexamic acid administration, in cases of mild TBI or as a bridge to neurosurgery. The appropriate timing of anticoagulant resumption was also discussed. Finally, we obtained an insight into the economic burden of TBI in patients on oral anticoagulants, and future directions on the management of this subpopulation of TBI patients were proposed. In this article, at the end of each section, a "take home message" is stated.

Background: The optimal management of patients taking oral anticoagulants who experience minor head injury (MHI) is unclear. The availability of validated protocols and reliable predictors of prognosis would be of great benefit. We investigated clinical factors as predictors of clinical outcomes and intracranial injury (ICI)., Methods: We conducted a single-cohort, prospective, observational study in an ED. Our structured clinical pathway included a first head CT scan, 24 h observation and a second CT scan. The primary outcome was the occurrence of MHI-related death or re-admission to ED at day +30. The secondary outcome was the rate of delayed ICI (dICI), defined as second positive CT scan after a first negative CT scan. We assessed some clinical predictors derived from guidelines and clinical prediction rules as potential risk factors for the outcomes., Results: 450 patients with a negative first CT scan who underwent a second CT scan composed our 'study population'. The rate of the primary outcome was 4%. The rate of the secondary outcome was 4.7%. Upon univariate and multivariate analysis no statistically significant predictors for the outcomes were found., Conclusions: Previous retrospective studies showed a lot of negative predictive factors for anticoagulated patients suffering a minor head injury. In our prospective study no clinical factors emerged as predictors of poor clinical outcomes and dICI. So, even if we confirmed a low rate of adverse outcomes, the best management of these patients in ED remains not so clear and future trials are needed., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Data in literature indicate that in patients suffering a minor head injury (MHI), biomarkers serum levels could be effective to predict the absence of intracranial injury (ICI) on head CT scan. Use of these biomarkers in case of patients taking oral anticoagulants who experience MHI is very limited. We investigated biomarkers as predictors of ICI in anticoagulated patients managed in an ED., Methods: We conducted a single-cohort, prospective, observational study in an ED. Our structured clinical pathway included a first head CT scan, 24 h observation and a second CT scan. The outcome was delayed ICI (dICI), defined as ICI on the second CT scan after a first negative CT scan. We assessed the sensitivity (SE), specificity (SP), negative predictive value (NNV) and positive predictive value (PPV) of the biomarkers S100B, NSE, GFAP, UCH-L1 and Alinity TBI in order to identify dICI., Results: Our study population was of 234 patients with a negative first CT scan who underwent a second CT scan. The rate of dICI was 4.7 %. The NPV for the detection of dICI were respectively (IC 95 %): S100B 92.7 % (86.0-96.8 %,); ubiquitin C-terminal hydrolase-L1 (UCH-L1) 91.8 % (83.8-96.6 %); glial fibrillary protein (GFP) 100 % (83.2-100 %); TBI 100 % (66.4-100 %). The AUC for the detection of dICI was 0.407 for S100B, 0.563 for neuron-specific enolase (NSE), 0.510 for UCH-L1 and 0.720 for glial fibrillary acidic protein (GFAP), respectively., Conclusions: The NPV of the analyzed biomarkers were high and they potentially could limit the number of head CT scan for detecting dICI in anticoagulated patients suffering MHI. GFAP and Alinity TBI seem to be effective to rule out a dCI, but future trials are needed., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Flexible bronchoscopy (FB) has become a standard of care for the triad of inspection, sampling, and treatment in critical care patients. It is an invaluable tool for diagnostic and therapeutic purposes in critically ill patients in intensive care unit (ICU). Less is known about its role outside the ICU, particularly in the intermediate care unit (IMCU), a specialized environment, where an intermediate grade of intensive care and monitoring between standard care unit and ICU is provided. In the IMCU, the leading indications for a diagnostic work-up are: To visualize airway system/obstructions, perform investigations to detect respiratory infections, and identify potential sources of hemoptysis. The main procedures for therapeutic purposes are secretion aspiration, mucus plug removal to solve atelectasis (total or lobar), and blood aspiration during hemoptysis. The decision to perform FB might depend on the balance between potential benefits and risks due to frailty of critically ill patients. Serious adverse events related to FB are relatively uncommon, but they may be due to lack of expertise or appropriate precautions. Finally, nowadays, during dramatic recent coronavirus disease 2019 (COVID-19) pandemic, the exact role of FB in COVID-19 patients admitted to IMCU has yet to be clearly defined. Hence, we provide a concise review on the role of FB in an IMCU setting, focusing on its indications, technical aspects and complications., Competing Interests: Conflict-of-interest statement: Authors certify that there is no conflict of interest related to the manuscript., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Little is known on prevalence of early return hospital admission of subjects with COVID-19 previously evaluated and discharged from emergency departments (EDs). This study aims to describe readmission rate within 14 days of patients with COVID-19 discharged from ED and to identify predictors of return hospital admission., Methods: We performed a retrospective cohort study of adult patients with COVID-19 discharged from two EDs. Return hospital admission was defined as an unscheduled return ED visit within 14 days after initial ED evaluation and discharge. We compared the group of patients who had a return hospital admission to those who did not. We also evaluated selected clinical characteristics (age, neutrophilia, SOFA, lactate dehydrogenase, C-reactive protein and D-dimer) associated with return hospital admission., Results: Of 283 patients included in the study, 65 (22.9%) had a return ED visit within 14 days. 32 of those patients (11%) were then hospitalized, while the remaining 33 were again discharged. Patients requiring a return hospital admission was significantly older, had higher pro-calcitonin and D-dimer levels. Major predictors of return hospital admission were cognitive impairment (OR 17.3 [CI 4.7-63.2]), P/F < 300 mmHg (OR 8.6 [CI 1.6-44.3]), being resident in geriatric care facility (OR 7.6 [CI 2.1-26.4]) and neutrophilia (OR 5.8 [CI 1.6-22.0])., Conclusion: Several factors are associated with 14-day return hospital admission in COVID-19 subjects. These should be considered when assessing discharge risk in ED clinical practice., (Copyright © 2021. Published by Elsevier Inc.)

There is a growing emphasis on including patients' perspectives on outcomes as a measure of quality care. This recent interest has spawned the rapid development and testing of patient-reported outcome measures (PROMs), through which patients report on their perception of the outcomes of the care they received. Their use has moved significantly from medical research toward applications in the clinical setting, quality measurement, and system accountability. While the use of as measures of clinical or treatment effectiveness, especially in chronic conditions, is widespread, their use in the emergency department (ED) setting is currently limited. In ED care, PROMs could offer promise since 80% of patients are discharged without any other way to track outcome. We explore the development and use of PROMs in publications on benchmarks and patient-centered care.

Background: The purpose of a patient-reported outcome (PRO) is to elicit the perspectives of patients and translate them into a reliable measurement questionnaire., Objectives: The objective of this cross-sectional study was to detect a set of PROs and PRO measurements (PROMs) about patients with isolated trauma of the limbs receiving emergency department (ED) care., Methods: A survey was performed in the ED using a questionnaire among the enrolled patients to identify which proposed outcomes were perceived as important by the patients according to their expectations., Results: Ninety-six consecutive patients were conveniently enrolled. For each item of the questionnaire, the percentage of patients who agreed to perceive it important were calculated. Three items were perceived important by almost 85% of the patients: getting an x-ray (91%; 95% CI: 88%-98%), obtaining a written therapy (94%; 95% CI: 87%-97%), and feeling the physicians' and nurses' empathy (97%; 95% CI: 91%-99%). The ED system was able to satisfy 2 of the 3 agreed PROs in at least 85% of the cases: getting an x-ray (97%; 95% CI: 91%-99%) and obtaining a written therapy (97%; 95% CI: 91%-99%). Moreover, in 30/96 patients (31%; 95% CI: 22%-41%), all the PROs were satisfied, and in 75/96 patients (78%; 95% CI: 69%-85%), all agreed PROs were satisfied., Conclusions: Our study shows an example of core of PROs proposed by the ED physicians and agreed by the patients. Moreover, we presented a set of PROMs which could be used to measure the quality of an ED., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Objective: To analyse the available evidence about the use of rituximab (RTX) and other biologic agents in eosinophilic granulomatosis with polyangiitis (EGPA) patients and to provide useful findings to inform the design of future, reliable clinical trials., Methods: A systematic review was performed. A systematic search was conducted in PubMed/MEDLINE, Scopus, Web of Science and the Cochrane library databases on RTX, and an extensive literature search was conducted on other biologic agents., Results: Forty-five papers pertinent to our questions were found: 16 retrospective cohort studies, 8 case series, 3 prospective cohort studies and 18 single case reports, for a total of 368 EGPA patients. More than 80% of evaluable patients achieved complete or partial remission with a tendency towards a higher rate of complete response in the pANCA-positive subgroup., Conclusion: Although the majority of the evaluable EGPA patients treated with RTX appears to achieve complete remission, we strongly believe that a number of sources of heterogeneity impair a clear interpretation of results and limit their transferability in clinical practice. Differences in design, enrolment criteria, outcome definition and measurement make a comparison among data obtained from studies on RTX and other biologic agents unreliable., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Patients with acute pulmonary embolism (PE) often have leg deep vein thrombosis (DVT); sometimes, however, a DVT is not detected (isolated PE, I-PE). We aimed at assessing the proportion of patients with I-PE, and their characteristics and clinical evolution compared to those with DVT with/without PE (DVT/PE)., Methods: Among 3573 patients included in the START2-Register for a venous thromboembolic event, 2880 (80.6%) had DVT/PE, the remaining I-PE (19.4%)., Results: Patients with I-PE were older [(≥75 years, OR 1.4 (95%CI 1.13-1.69)], and more frequently females [OR 1.4 (1.19-1.67)]. Young females (aged ≤ 50 years) with an index event occurring during hormonal contraception (HC), were more prevalent in I-PE [OR 1.96 (1.26-3.03)]. At multivariate analysis, age > 75 years, female sex, heart failure, cancer and use of HC were risk factors significantly associated with I-PE, whereas thrombophilic alterations were associated with DVT/PE. During a follow-up of 4504 years (during anticoagulation), the rate of bleeding events was 1.1% patient/years and 1.0% patient/years in I-PE and DVT/PE, respectively. Venous thromboembolic events were equally prevalent in DVT/PE or I-PE (1.94% vs 0.86%, ns), whereas arterial complications were more prevalent in the latter group (1.01% vs 0.28%, p = 0.008)., Conclusion: I-PE and DVT/PE have important differences. Older age, female sex, heart failure and cancer, were risk factors for I-PE; thrombophilic alterations were associated with DVT/PE. HC use was more frequent in the I-PE group. The prevalence of arterial complications was higher in patients with I-PE. Further studies, specifically designed on this issue, are warranted., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Natural history and outcomes of patients with pulmonary embolism (PE) without typical symptoms (atypical PE) remain unclear. The aim of the study is to compare the clinical characteristics and the prognosis between typical PE and atypical PE., Methods: We retrospectively analyzed data from consecutive patients admitted to the Emergency Department (ED) because of a diagnosis of PE and classified them in two groups: typical PE and atypical PE. We defined PE to be typical in presence of almost one of the following symptoms or signs: dyspnea, chest pain, hemoptysis or signs of deep vein thrombosis., Results: Of the 191 patients with PE, 154 (81%) had typical PE and 37 (19%) had atypical PE. Patients with atypical and typical PE seemed to had similar prognostic factor such as high risk sPESI (73% vs 65%, p=0.3), right ventricular dysfunction (30% vs 26%, p=0.6) and central PE at chest CT scan (38% vs 36%, p=0.8). The rate of 30 day mortality was 7% in the typical group and 8% in the atypical group (p=0.8). The length of stay in hospital was the same in the two groups (6 days; p=0.2)., Conclusions: We found that atypical and typical PE seem to be related diseases with a similar short term prognosis. Therefore, we could speculate that a missed diagnosis of PE in ED could expose the patients to a worsen prognosis. Further perspective studies are required for better investigate this diagnostic challenge.

Study Objective: The optimal management of patients receiving heparin, warfarin or direct anti-coagulant therapy who experience spontaneous, severe, life-threatening soft-tissue hemorrhage (SSTH) is unclear. The purpose of this study is to investigate efficacy and safety of the interventional protocol implemented in our department., Methods: In this retrospective cohort study, we analyzed data from 80 consecutive patients with SSTH secondary to anticoagulation therapy diagnosed by the appropriate computed tomography scan. All patients received a structured clinical pathway, including aggressive resuscitation, reversal of coagulopathy when indicated, Interventional Radiology procedures by transcatheter embolization (TE), clinical observation and repeated laboratory controls., Results: We enrolled 80 patients from 2013 to 2017. Angiography was performed in 60 patients (75%). It revealed the bleeding site in 46 cases, and a TE was performed in all. The rates of technical success of TE, primary clinical success and bleeding control were 98% (45/46), 91% (73/80) and 89% (71/80) respectively. In 5 patients (6%) the control of the bleeding was obtained with a second TE. Short-term and 30-day mortality was 5% (4 patients) and 11% (9 patients), respectively. No adverse events were observed., Conclusion: A structured clinical pathway, including TE seems to be an effective and safe method to manage the patients with SSTH due to anticoagulant treatment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The aim of this paper was to evaluate socio-economic factors associated to poor primary care utilization by studying two specific subjects: the hospital readmission rate, and the use of the Emergency Department (ED) for non-urgent visits., Methods: The study was carried out by the analysis of administrative database for hospital readmission and with a specific survey for non-urgent ED use., Results: Among the 416,698 sampled admissions, 6.39% (95% CI, 6.32-6.47) of re-admissions have been registered; the distribution shows a high frequency of events in the age 65-84 years group, and in the intermediate care hospitals (51.97%; 95%CI 51.37-52.57). The regression model has shown the significant role played by age, type of structure (geriatric acute care), and deprivation index of the area of residence on the readmission, however, after adjusting for the intensity of primary care, the role of deprivation was no more significant. Non-urgent ED visits accounted for the 12.10%, (95%CI 9.38-15.27) of the total number of respondents to the questionnaire (N = 504). The likelihood of performing a non-urgent ED visit was higher among patients aged <65 years (OR 3.2, 95%CI 1.3-7.8 p = 0.008), while it was lower among those perceiving as urgent their health problem (OR 0.50, 95%CI 0.30-0.90)., Conclusions: In the Italian context repeated readmissions and ED utilization are linked to different trajectories, besides the increasing age and comorbidity of patients are the factors that are related to repeated admissions, the self-perceived trust in diagnostic technologies is an important risk factor in determining ED visits. Better use of public national health care service is mandatory, since its correct utilization is associated to increasing equity and better health care utilization.

Introduction: Burnout syndrome (BOS) associated with stress has been documented in health care professionals in many specialties. The emergency department and the pre-hospital healthcare services are highly stressful environments. Little is known about the BOS in critical care nursing staff. The objective of the study is to compare the incidence of BOS and its three domains, namely, emotional exhaustion, depersonalization and reduced professional accomplishment, in two cohorts of critical care nurses: a pre-hospital and a hospital emergency service., Methods: A survey using a questionnaire (the Maslach Burnout Inventory-General Survey, MBI-GS), among nurses of two Italian emergency services has been performed: a hospital emergency service (HES, Emergency Department or "Pronto Soccorso") and a pre-hospital emergency service (PHES, territorial healthcare service or "Centrale Operativa 118")., Results: All 60 nurses surveyed (82% female) filled the questionnaires. BOS-related symptoms have been identified in at least 50% of the nurses in the HES: 50% suffered a medium-high emotional exhaustion, 75% had a medium-high depersonalization and 92.5% had a medium-high reduced professional accomplishment. Among the PEHS nurses, BOS-related symptoms have been identified in at least 60% of the respondents: 60% had a medium-high emotional exhaustion, 70% had a medium-high depersonalization and 95% had a medium-high reduced professional accomplishment. Moreover, the likelihood that a nurse has a severe BOS, that is at least one degree of high burnout or ≥2 degrees of medium burnout, is significantly higher in the group of the PHES than in the HES (90% vs 60%, p <0.02)., Conclusion: At least two-thirds of critical care nursing staff had a severe BOS. The incidence of BOS appeared to be similar among PHES and HES nurses with a higher trend for the former. Further interventional studies are needed to investigate the determinants of BOS among critical care nurses and the potentially preventive strategies.

Aim: The stone disease of the urinary tract (urolithiasis) is a growing disease. The identification of metabolic disorders, treatable with prophylactic therapy, appears to be clinically important. The aim of this study was the analysis of metabolic disorders that promote and support the urolithiasis in a cohort of patients with renal colic at an Emergency Department., Methods: In this prospective case series, we enrolled consecutive patients with renal colic treated at an Emergency Department within a Regional Teaching Hospital. We implemented a structured metabolic evaluation, which included blood chemistry studies, stone analysis and a 24-hour urine collection. We then evaluated the frequency of metabolic abnormalities alone or in combination., Results: We enrolled 39 patients whit renal colic and a diagnosis of urolithiasis: 21 (54%) were males and the median age was 43.6 years (range 20-70). The most frequently observed type of stone was that of calcium oxalate (74%). Hypomagnesiuria was the most common metabolic abnormality found at the 24-hour urine collection (22/39, 56%), followed by hypocalciuria (31%), hypernatruria (20%), hyperuricuria (18%) and hyperoxaluria (15%). Among the associations of metabolic abnormalities, the hypocalciuria /hypomagnesuria was that observed with higher frequency (23%)., Conclusion: We report an incidence of hypomagnesiuria (60%) in patients with renal colic higher than has ever been described in the literature. This result could be of importance in the knowledge of the pathogenesis of the urolithiasis and could have interesting implications in clinical practice.

Study Objective: Patients receiving warfarin who experience minor head injury are at risk of intracranial hemorrhage, and optimal management after a single head computed tomography (CT) scan is unclear. We evaluate a protocol of 24-hour observation followed by a second head CT scan., Methods: In this prospective case series, we enrolled consecutive patients receiving warfarin and showing no intracranial lesions on a first CT scan after minor head injury treated at a Level II trauma center. We implemented a structured clinical pathway, including 24-hour observation and a CT scan performed before discharge. We then evaluated the frequency of death, admission, neurosurgery, and delayed intracranial hemorrhage., Results: We enrolled and observed 97 consecutive patients. Ten refused the second CT scan and were well during 30-day follow-up. Repeated CT scanning in the remaining 87 patients revealed a new hemorrhage lesion in 5 (6%), with 3 subsequently hospitalized and 1 receiving craniotomy. Two patients discharged after completing the study protocol with 2 negative CT scan results were admitted 2 and 8 days later with symptomatic subdural hematomas; neither received surgery. Two of the 5 patients with delayed bleeding at 24 hours had an initial international normalized ratio greater than 3.0, as did both patients with delayed bleeding beyond 24 hours. The relative risk of delayed hemorrhage with an initial international normalized ratio greater than 3.0 was 14 (95% confidence interval 4 to 49)., Conclusion: For patients receiving warfarin who experience minor head injury and have a negative initial head CT scan result, a protocol of 24-hour observation followed by a second CT scan will identify most occurrences of delayed bleeding. An initial international normalized ratio greater than 3 suggests higher risk., (Copyright © 2011 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

Pediatric emergencies have a relatively low incidence compared to the total number of pre-hospital events. The quality of emergency care for pediatric patients can be improved by specific training, a dedicated team and uniformity of pediatric protocols. The aim of this study is to assess how nurses perceive pediatric emergencies in a non-hospital environment by means of two questionnaires issued to two cohorts of nurses working on ambulances. The results of the study show that nursing care of pediatric patients in critical situations seems to depend on adequate training, not only formal but also with simulations, paying particular attention to the emotional situation nurses have to face, and complete equipment of the ambulance and emergency personnel.

A hernia of Morgagni (also called hernia of Morgagni-Larrey) is a congenital herniation of abdominal contents into the thoracic cavity through a retrosternal diaphragmatic defect. The Morgagni hernia can create uncertainty in its diagnosis and difficulty for subsequent treatment. If after clinical examination and x-ray we suspect the hernia, computed tomography imaging should be the desired imaging method to confirm the diagnosis. Surgery is the only definitive treatment. When a patient presents signs and symptoms of incarceration or strangulation, emergency surgery is required. We report the first life-threatening case of an association between a hernia of Morgagni and a mediastinal lipoma. We present an adult patient with mediastinal lipoma and a right incarcerated hernia of Morgagni with engagement of the stomach, the duodenum and the transverse colon, successfully treated without complications. To our knowledge, this is the first report of an association between those two rare entities in an acute setting. We discuss the differential diagnosis and physiopathology of the condition, referring to published reports.

The urolithiasis is a growing disease because of the changes in dietary habits and in he general life style. Urolithiasis is characterized by the recurrent clinical manifestation and possible effect of structural damage of the kidneys and of the urinary tract ast well as the potential increase in systemic blood pressure. Moreover, frequent need for medical cure and invasive urological treatment exposes the patient to the complications of such procedures. The lithogenic process involves a wide number of systemic pathologies that are often undiagnosed. However, once identified they can be treated more precisely having an impact on the stone's forming process. For these reasons, prevention of new urolithiasis in patients, and in particular in those with high risk, appears to be clinically important. Metaphylaxis can be differentiated in two ways: "general metaphylaxis" in patients with lithiasis of the urinary tract, and "specific metaphylaxis" meant for patients with risk factors for recurrent calculosis. The aim of this narrative review is to present an algorithm for clinical practice for patients that have undergone one or more attacks of renal/ureteral colic from lithiasis in order to prevent further attacks. As such, this review deals with a method of secondary prevention (prophylaxis) that aims at identifying and correcting metabolic disorders (from which the term metaphylaxis comes) that favor and support the lithogenic process in the urinary tract.

Testicular cancer is the most common malignancy in men aged 15-35 years. Histologically, testicular germ-cell tumors have two main subtypes: pure seminoma and nonseminoma. Knowing the histopathological tumor type and detecting the relevant prognostic factors helps to guide the subsequent therapeutic course. At present there are no recommendations for testicular cancer screening in healthy young men, even among men showing high risk; however, a testicular cancer should be diagnosed as soon as a young man presents with suggestive signs and symptoms. Furthermore, thanks to highly effective treatments including surgery, chemotherapy, and radiation therapy, it is very important to effectively manage secondary prevention and improve these patients' quality of life. Secondary prevention of relapses or secondary malignancy onsets should be carried out through a regular follow-up of the patient; in selected cases of positive family history, it is possible to perform genome-wide analyses aiming at searching the genes possibly causing testicular germ-cell tumor in affected first-degree male relatives. Long-term therapies can yield infertility and sexual dysfunction, issues gaining more and more importance from a clinical point of view. Sperm cryopreservation should be systematically offered to all requiring patients; moreover, screening for gonadal dysfunction should be considered in the follow-up of testicular cancer survivors, with the aim of hormone supplementation in symptomatic patients.

Objective: Intravenous (IV) injection is currently the normal method for transplanting hematopoietic cells. However, the problem of seeding efficiency and homing is relevant especially when a limited number of stem cells is available. Intra-bone marrow (IBM) injection of bone marrow cells (BMCs) may overcome this problem., Materials and Methods: Irradiated (750 cGy) C57BL/6J mice were transplanted with 1 x 10(5) BMCs harvested from transgenic mice expressing an enhanced version of the green fluorescent protein (EGFP+) via IBM or with 1 x 10(6) EGFP+ BMCs via IV. Irradiated (320 cGy) NOD/SCID mice were transplanted with 1 x 10(6) human cord blood (CB) cells via IBM or with 1 x 10(7) human CB cells via IV., Results: In C57BL/6J mice after 90 days, the fraction of EGFP+ cells harvested was 37% and 53% in IV-treated and IBM-treated (contralateral tibia and femur in the IBM) mice, respectively: the expansion folds were 114 and 1760, respectively. In NOD/SCID mice, the percentages of CD45+ cells and CD45+/CD34+ cells were, at 30 days, 3.3% and 0.3% in IV-treated mice, and 4.4% and 1.1% in IBM-treated mice. At 60 days, the percentages of CD45+ cells and CD45+/CD34+ cells were 2.1% and 0.3% in IV-treated mice and 1.4% and 0.4% in IBM-treated mice. At day 90 the percentages of CD45+ cells and CD45+/CD34+ cells were 3% and 0.3% in IV-treated mice and 2.3% and 0.4% in IBM-treated mice., Conclusion: Our data demonstrate that IBM transplantation is associated with a seeding efficiency 15 times greater than IV transplantation. IBM transplantation may improve the results of transplant and may be useful in several settings: 1) when a limited number of hematopoietic progenitors are available; and 2) in experiments aiming to place in the bone marrow stem cells of other lineages (CNS, muscle, etc.).

This study compared iloprost and nifedipine to ascertain whether they could improve parameters of endothelial and platelet functions in the treatment of Raynaud's phenomenon secondary to systemic sclerosis. Thirteen patients affected by systemic sclerosis were treated with intravenous infusion of iloprost, and 7 patients were treated with oral nifedipine. Blood samples were taken at baseline and after 6 and 12 months of therapy to assess main serological indexes of endothelial damage, thrombin activation, fibrinolysis, as well as natural inhibitors of coagulation. After 12 months of therapy, the patients treated with iloprost had a significant decrease in thrombomodulin levels (p = 0.02) and a significant increase in tissue-plasminogen activator levels (p = 0.007), in comparison with the patients taking nifedipine (p = 0.007). Moreover, patients treated with nifedipine showed increased levels of thrombin-antithrombin complex after 12 months of therapy in comparison with baseline values (p = 0.03) and in comparison with the values of the patients treated with iloprost over the same period (p = 0.05). These preliminary results thus seem to indicate that iloprost plays an important, if at least partial, role in the protection and restoration of endothelial integrity in patients with systemic sclerosis.